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Karger Publishers, Acta Haematologica, 4(133), p. 354-364, 2015

DOI: 10.1159/000369446

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Apoptosis-Related Gene Expression Profile in Chronic Myeloid Leukemia Patients after Imatinib Mesylate and Dasatinib Therapy

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

<b><i>Background/Aims:</i></b> We investigated the effects of tyrosine kinase inhibitors (TKIs) on the expression of apoptosis-related genes (BCL-2 and death receptor family members) in chronic myeloid leukemia (CML) patients. <b><i>Methods:</i></b> Peripheral blood mononuclear cells from 32 healthy subjects and 26 CML patients were evaluated before and after treatment with imatinib mesylate (IM) and dasatinib (DAS) by quantitative PCR. <b><i>Results:</i></b> Anti-apoptotic genes <i>(c-FLIP </i>and<i> MCL-1)</i> were overexpressed and the pro-apoptotic <i>BIK </i>was reduced in CML patients. Expression of <i>BMF, A1, c-FLIP, MCL-1, CIAP-2 </i>and <i>CIAP-1 </i>was modulated by DAS. In IM-resistant patients, expression of <i>A1, c-FLIP, CIAP-1</i> and <i>MCL-1 </i>was upregulated, and <i>BCL-2</i>,<i> CIAP-2</i>,<i> BAK, BAX, BIK </i>and <i>FASL </i>expression was downregulated. <b><i>Conclusion:</i></b> Taken together, our results point out that, in CML, DAS interferes with the apoptotic machinery regulation. In addition, the data suggest that apoptosis-related gene expression profiles are associated with primary resistance to IM.